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jimmylegs wrote:http://www.thisisms.com/forum/natural-a ... ml#p253767
excerpt:
"Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. “Western” dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies. This could contribute to multiple pathologies including autoimmune and inflammatory diseases."

IgA production is also inhibited by EBV that "works" on the Peyer's Patches. Over 10's of millions of years of evolution, the virus has learned how to maximise its chances. This points to a viral dimension of autoimmunity and multiple pathologies. This again confirms the bigger overall picture on http://www.thisisms.com/forum/general-d ... ml#p251748

quote from the abstract: The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including ...., and modulation of systemic or central nervous system-specific immunity. unquote

Of course. Weakened immunity of the nasopharynx (CCSVI may be a contributing factor here) leads to herpes viral spreading. This may initiate a long cascade of events that eventually leads to inflammatory and -later on- to progressive MS. This is yet another publication that fully fits the skeleton at http://www.thisisms.com/forum/general-d ... ml#p251748 (see e.g. step 2 viral culprit where hypoperfusion weakens the immunity of the nasopharynx)

A bad gut leads to a deficient methylation/failure of epigenetic regulation and cellular expression.
The cross reaction of endothelial cells with B cells leads to a biochemical reaction which in turn leads to elevated peroxynitrite and mounting oxidative stress at cellular level.
See also steps 5 and 6 of: http://www.thisisms.com/forum/general-d ... ml#p251748

How long do I have to go on before the professional sector starts to see the bigger picture, before they start to see that there is something like an overarching concept ?
Whose attention should be drawn to get professionals embrace the big thinking?

If the view proposed in this article can be shown to be correct, then we will be in a new era in medicine. That will be true even if the relevance of this approach is limited to such diseases as CFS/ME, MCS, and FM. If other proposed NO/ONOO− cycle diseases, such as tinnitus, Parkinson’s, Alzheimers, ALS, asthma, autism, and MS, can also be cured by this approach, then the impact on medicine will be comparable to the previous biggest therapeutic breakthrough, the development of wide-spectrum antibiotics.

Is this all delusional optimism? Clearly, we won’t know until we look. But what we do know is that all of these diseases are chronic diseases, with cases of each apparently initiated by stressors that should be able to initiate the cycle. And we have evidence with all of them for important roles of such cycle elements as oxidative stress, inflammatory biochemistry, mitochondrial dysfunction, and excessive NMDA activity. Where they have been looked at, we also have evidence for BH4 depletion and NF-κB elevation. It is difficult to see how these cycle elements could be involved unless the NO/ONOO− cycle or something very similar to it is not central to the etiology of these diseases.

But his view on the cellular biochemistry needs to be augmented with several other dimensions. And connections need to be made. With the viral dimension and SNPs, the epigenetics/cellular expression and the gut, the EBV B cells and their superoxide generation. All these issues were ingredients of the ACTRIMS 2017 Forum. And of course, for MS, we need to add in CCSVI, a breach of the BBB and viral spreading into the CNS.

We must knit all these issues or interdependent innovations together. It is then and only then that we get a complete and highly plausible picture. And then, as Martin Pall says, we will be in a new era in medicine, with an impact on medicine comparable to the previous biggest therapeutic breakthrough, the development of wide-spectrum antibiotics.

Every system has its own inertia. While the weight of the status quo is immense. This prevents change, change won't come easy and will always be too slow for us. I guess that explains my frustration.

Last edited by Leonard on Mon Jan 28, 2019 1:23 am, edited 2 times in total.

The explanation for that comorbidity lies in the oxidative stress cycle that varies among different patients depending on their cellular SNPs (with an anti-viral signalling function which is genetically determined) and the primarily local nature of the cycle. Different tissue localization of the oxidative stress cycle from one case to another produces different tissue impact and therefore different symptoms and often different diagnoses. Chronic diseases then often occur together in different patients (like here asthma and MS) for the reason that, besides the SNPs in different tissues, the patients lack adequate epigenetic control by the gut. At that point, cells that have been captured by the virus (because of insufficient anti viral signalling by SNPs, in different tissues somewhat genetically determined, sometimes they are referred to as permissible cells) come to expression leading to a cross reaction with B cells and superoxide to what is often referred to as an autoimmune response. This is followed by oxidative stress, peroxynitrite, the cycle.
For further reference, see Martin Pall's paper on https://www.clinicaleducation.org/resou ... -a-review/

With this view, I think we've arrived at a total breakthrough for most autoimmune diseases and, in combination with the above skeleton, of course for MS. Incidently, also Heart Failure may be explained by such mechanism.

And we've arrived at a point where one may start to wonder how useful old work (e.g. published articles on MS) really is or has become. In fact, against the background of this new view, I think most old work in the old verticalised medical paradigm is just fake. viewtopic.php?f=1&t=30677

We know now what causes autoimmune diseases. We know to a certain level of detail what is MS and what causes it. Now that the technicalities of the diseases are known, we can work towards more effective therapies. But this requires change, change of the system.

Furthermore, this article that I find on the other thread makes quite compelling arguments why our system needs change. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140370/ on The Crisis of Capitalism and the Marketisation of Health Care: the Implications for Public Health Professionals

It is here that we run into problems. It is not the lack of medical technical understanding; it is the systemic issues that prevent change.

So many institutions and so many people from the health profession, science, commerce and government have so much invested in the current system, and therefore so much to loose by change. It is for this reason that we are not just dealing with problems of medical complexity but need to address political, economic and social issues.

It should be stressed of course that we are indebted to many of these institutions and individuals for so much progress over the last century. However, their very success, translated into power and influence, is now causing the problems.

As clinical medicine grew from strength to strength and its institutions became very grand and powerful, they have largely determined the shape of the whole health industry and how we think about health. They consolidated the power of the clinical medical profession.

But like the first antibiotics ended the grip of pneumonia and with that changed the course of history, the new insights in autoimmunity are set to change the course of history again, towards a whole new paradigm in medicine. This will not be a smooth transition or a gentle glide into the new world. Due to the inertia of the system, change will be disruptive and difficult, and resistance will be met everywhere. Powerful forces are opposing change, the scene is set for conflict.

Notwithstanding, with all current research e.g. into the role of the gut and the epigenetics and with patients becoming ever more vocal and networked (as here on TIMS) and sometimes even dictating new courses for clinical practice (e.g. on HSCT in Belgium), I am sure we are travelling in the right direction and change will happen. The big question for us now is how to accelerate the change, smooth its path and make sure that not too much damage is done on the way. In other words, how to make this transition as fast and comfortably as possible.

I think we need to stop having compartmentalized discussions in old vertical medical pillars and involve thousands of (young) people discovering the future for themselves as they help to create it. We need to do that in a more horizontal framework in layers as virology and immunology, the gut and epigenetics and microcellular biochemistry and oxidative stress whilst bringing together at the same time these interdependent layers.

I think it will need to be a process that I sometimes compare with the liberalization of the telecoms sector that was launched in Europe in 1987 (I was deeply involved). The 1987 Green Paper successfully defined a framework within which action could develop, leading to full liberalization of telecommunications in the European Union by 1998. At around more or less the same time, in the US the old AT&T was divested, the telecoms industry opened up and the Internet emerged. Under the rules of the WTO, the liberalisation process spilled over to many other part of the world. The subsequent decades saw an enormous expansion of services and entirely new industry dynamics. It is the medical world now that needs to be opened up in a similar way.https://www.emeraldinsight.com/doi/abs/ ... 1311305399

Last edited by Leonard on Fri Feb 01, 2019 1:36 am, edited 10 times in total.

As we have seen in the last few postings, the herpes virus causes many more diseases, including autoimmune diseases.
MS is then a special case as explained in the first steps of the above skeleton. Venous obstruction in the neck (CCSVI), a breach of the BBB, compromised immunity and herpes viral spreading into the CNS are definitely contributing factors in its inception.

Rather than SNPs, for MS vascular narrowings in the neck seem to play an important role. Zivadinov/Buffalo has shown that 80-85% of patients with MS have CCSVI. Conversely, Zamboni found that over 90% of the young people he diagnosed with vascular narrowings in the neck had developed MS 20 years later.

Last edited by Leonard on Tue Feb 12, 2019 8:54 am, edited 3 times in total.

Leonard, thanks for your honest reply. My father was diagnosed with MS about 45 years ago and frankly little more is known about MS now than back then. There are many reasonable theories but really no definitive details. Someday this will change...

I remember an earlier study on the effect of statins that was reported in the Lancet and that can be found somewhere back on this thread. The findings of Swank (low consumption of saturated fats slow progression) fall in the same category.

Clearly, and as confirmed by the results of the study, the statins don't work on the inflammatory part of MS but help slow progression.

The virus infection and spreading was there all the time.
Normally the virus is latent and the immune system is tolerant.

The microbiome gets ever worse.
Our modern lifestyle and diet are contributing factors.
Also with age EBV spreads and affects the Peyers' Patches reducing IgA and gut immunity.

The epigenetic regulation deteriorates (methylation cycle lost) and cells come to expression.
Herpes viral epitopes that are expressed in cells and immune cells cross react and cause superoxide.
This causes localised oxidative stress in tissue (that is in "permissible" cells virally loaded which is SNP determined).

This explains the scourge of all sort autoimmune diseases including MS.
For MS, vascular narrowing in the neck (CCSVI) is an extra contributing factor compromising the BBB and allowing viral anchoring in specific places in the CNS.

Last edited by Leonard on Mon Feb 04, 2019 6:01 am, edited 2 times in total.

If the methylation cycle is restored (normally should be done by restoring the gut function but here is it is done by oral administration), cellular expression will be down and the autoimmune reaction will come to a halt. I don't exclude the possibility that some remyelination may occur at that point.

See also the previous posting on the loss of the methylation cycle and how this fits in the overall picture.

If we assume for a moment that all autoimmune diseases originate from the same underlying mechanism (i.e. B cells that cross react with viral epitopes after epigenetic expression and release superoxide, giving rise to highly localised oxidative stress), then diabetes 2 and other autoimmune diseases could (should) be tackled by addressing that underlying mechanism.

The above article from July 2018 suggests precisely this, i.e. that the very widely used medication for diabetes 2 (metformin) could in fact be useful for a whole range of other autoimmune/aging diseases. Quote from the article: There is evidence that these alterations influence the epigenome and gene expression, and may contribute to the antidiabetic properties of metformin and, potentially, may protect against cancer, cardiovascular disease, cognitive decline and aging. Other articles study the role of metformin in cellular methylation.

And conversely, that all these autoimmune/aging diseases originate from a common underlying mechanism which again would seem to confirm the broad picture that is emerging here, that is the total breakthrough that is on the horizon.

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